Objective
Nonsense-mediated mRNA decay (NMD) is an essential mechanism controlling translation in the eukaryotic cell. NMD ascertains accurate expression of the genetic information by quality controlling messenger RNA (mRNA). During translation, NMD factors recognize and target to degradation aberrant mRNAs that have a premature stop codon (PTC) and that would otherwise lead to the production of truncated proteins which could be harmful for the cell. A wide range of genetic diseases have their origin in the mechanisms of NMD. Discrimination of a PTC from a correct termination codon depends on splicing and translation, and it is the first and foremost step in human NMD. The molecular mechanism of this process remains elusive to date.
In the research proposed, I will undertake to elucidate the molecular basis of translation termination and induction of NMD. I will study complexes involved in human translation termination at a normal stop codon and involved in NMD. I will employ an array of innovative techniques including recombinant production of human protein complexes by the MultiBac system, mammalian in vitro translation, mass spectrometry for detecting relevant protein modifications, biophysical techniques, mutational analyses and RNA-interference experiments. Stable ribosomal complexes with termination factors and complexes of NMD factors will be used for structure determination by cryo-electron microscopy. State-of-the-art image processing will be applied to address the inherent heterogeneity of the complexes. Hybrid approaches will allow the combination of cryo-EM structures with existing high-resolution structures of factors involved for generation of quasi-atomic models thereby visualizing molecular mechanisms of NMD action. This interdisciplinary work will foster our understanding at a molecular level of a paramount step in mRNA quality control, which is a vital prerequisite for the development of new treatment strategies in NMD-related diseases.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- social sciences sociology social issues social inequalities
- natural sciences biological sciences genetics RNA
- natural sciences chemical sciences analytical chemistry mass spectrometry
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2011-StG_20101109
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
69117 Heidelberg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.